Abstract 3265: Dual specificity phosphatase 4 gene expression in triple negative breast cancer

Abstract

Abstract Background Triple negative breast cancer (TNBC) is an aggressive cancer with limited treatment options. A recent report suggested that dual specificity phosphatase 4 (DUSP4) may be a potential marker of chemotherapy resistance for TNBC. Methods We measured the DUSP4 gene expression levels in breast cancer tissue from 469 TNBC patients who participated in the Shanghai Breast Cancer Survival Study and evaluated their association with breast cancer recurrence/breast cancer mortality and total mortality. Study participants were diagnosed with incident breast cancer between March 2002 and April 2006 and aged between 20 and 75 years. Information on breast cancer diagnosis and treatment, as well as demographic, lifestyle, and disease progression information, were collected approximately 6 months after cancer diagnosis and reassessed at 18, 36, and 60 months after diagnosis in follow-up interviews. Expression levels of transcript variant 1 (NM_001394) and transcript variant 2 (NM_057158) of DUSP4 gene were measured by the NanoString nCounter assay using RNA obtained from formalin-fixed, paraffin-embedded tissue sections. Cox regression analysis was applied in the data analyses with adjustment for clinical and demographic factors. Results Of the 469 TNBC participants in this study, 100 deaths and 92 recurrences/breast cancer deaths were documented over a median follow-up of 5.3 years (range, 0.7-8.9 years). The expression of the two DUSP4 isoforms were highly correlated (r=0.76). Low DUSP4, particularly variant 1 (NM_001394), expression levels were associated with increased recurrence/breast cancer mortality and overall mortality. After adjustment for age at diagnosis and TNM stage, the hazard ratios comparing those with DUSP4 (variant 1) expression levels below the median to those above the median were 1.97 (95% confidence interval (CI): 1.27, 3.05) for recurrence/breast cancer mortality and 2.09 (95% CI: 1.38, 3.17) for overall mortality. Adjustment for expression levels of MKI67 and TP53, common treatment types, breast cancer subtype, or grade did not materially alter the observed association. Conclusion Low DUSP4 expression levels predict recurrence and mortality in TNBC patients independently from known clinical and molecular predictors. Citation Format: Michelle L. Baglia, Qiuyin Cai, Ying Zheng, Jie Wu, Yinghao Su, Fei Ye, Ping-Ping Bao, Hui Cai, Zhiguo Zhao, Wei Zheng, Wei Lu, Xiao-Ou Shu. Dual specificity phosphatase 4 gene expression in triple negative breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3265. doi:10.1158/1538-7445.AM2014-3265